Lenalidomide Dose Escalation Combined With Rituximab/Fludarabine in Untreated CLL - Full Text View

Purpose

The aim of this study is to determine the maximal tolerated dose level of lenalidomide combined with fludarabine/rituximab in the therapy of patients with previously untreated CD20-positive chronic lymphocytic leukemia. Following a dose escalation phase lenalidomide will be given at the pre-determined maximum tolerated dose in combination with rituximab to further determine the efficacy and tolerability of this regimen.

Condition	Intervention	Phase
Leukemia, Lymphocytic, Chronic, B-Cell	Drug: Lenalidomide Drug: Fludarabine Biological: Rituximab	Phase I Phase II

MedlinePlus related topics:

Leukemia, Adult Acute Leukemia, Adult Chronic

ChemIDplus related topics:

Fludarabine Fludarabine monophosphate Rituximab Lenalidomide CC 5013

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety Study

Official Title:	Fludarabine/Rituximab Combined With Escalating Doses of Lenalidomide Followed by Rituximab/Lenalidomide in Untreated Chronic Lymphocytic Leukemia (CLL) - a Dose-Finding Study With Concomitant Evaluation of Safety and Efficacy.

Further study details as provided by Arbeitsgemeinschaft medikamentoese Tumortherapie:

Primary Outcome Measures:

Lenalidomide Maximum Tolerated Dose [ Time Frame: Dose escalation stage ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Safety profile of Lenalidomide/Fludarabine/Rituximab treatment [ Time Frame: Study Duration ] [ Designated as safety issue: Yes ]
Safety Profile of Lenalidomide/Rituximab [ Time Frame: Study duration ] [ Designated as safety issue: Yes ]
Response rate for Lenalidomide/Fludarabine/Rituximab combination treatment [ Time Frame: Dose escalation stage ] [ Designated as safety issue: No ]
Response rate for Lenalidomide/Rituximab combination therapy [ Time Frame: Study Duration ] [ Designated as safety issue: No ]
Response rate by 4-colour flow cytometric MRD analysis [ Time Frame: Study Duration ] [ Designated as safety issue: No ]
Changes in Quality of Life scores [ Time Frame: Study Duration ] [ Designated as safety issue: No ]
Risk factors and clonal evolution [ Time Frame: Study Duration ] [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	September 2008
Estimated Study Completion Date:	March 2011
Estimated Primary Completion Date:	March 2011 (Final data collection date for primary outcome measure)

Arms

Assigned Interventions

Treatment Arm: Experimental

Lenalidomide Dose Escalation combined with Fludarabine/Rituximab followed by maximum tolerated lenalidomide dose/Rituximab maintenance therapy

Drug: Lenalidomide

Dose escalation stage: starting dose 2.5mg/d, dose escalation via 5/10/15/20/25 mg/d every 28 days if no dose-limiting toxicity.

During maintenance stage dosing on days 1-28 for max. 6 months at maximum tolerated dose reached during dose escalation stage.

Drug: Fludarabine

25 mg/m2 i.v. d1-3 or 40 mg/m2 po d1-3 every 28 days for 6 cycles during dose escalation stage.

Biological: Rituximab

Dose escalation stage: 375 mg/m2 i.v. d4 Cycle 1, 500 mg/m2 i.v. d1 Cycles 2-6.

Maintenance stage: 375 mg/m2 i.v. at 2/4/6 months after end of escalation stage.

Detailed Description:

This is a non-randomized, multicenter, open-label, single-arm Phase I/II study in patients with previously untreated CD20-positive CLL. Phase I of the study will evaluate the maximal tolerated lenalidomide dose level in combination with fludarabine/rituximab chemoimmunotherapy in 10 patients. Phase II will determine efficacy using the combination in the previously defined maximal tolerated dose. Both phases will be followed by a maintenance phase evaluating the tolerability and possibility to further improve response quality.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

B-CLL (CD23+, CD5+, CD19+, CD20+)
Treatment indication according to NCI criteria
Age >= 18 yrs
No previous treatment of CLL by chemo-, radio- or immunotherapy
Life expectancy > 6 months
Written informed consent
Women of non-childbearing potential or women of childbearing potential and men using effective contraception

Exclusion Criteria:

Active bacterial, viral or fungal infection
Positivity for HIV, Hepatitis B or C
Reduce organ functions and bone marrow dysfunction not due to CLL
Creatinine clearance below 30 ml/min
Patients with medical conditions requiring long-term use of systemic corticosteroids during study treatment
Patients with a history of severe cardiac disease
Other known co-morbidity with the potential to dominate survival
Transformation to aggressive B-cell malignancy
Known hypersensitivity to humanised monoclonal antibodies or any of the study drugs
Pregnant or breast-feeding women
Any co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00738829

Contacts


Contact: Richard Greil, Prof. Dr.	+436624482 ext 2879	r.greil@salk.at

Contact: Alexander Egle, Ass.Prof. Dr.	+436624482 ext 2879	a.egle@salk.at

Locations


Austria
	A.ö. Landeskrankenhaus Leoben	Not yet recruiting
	Leoben, Austria, A-8700
	Contact: Felix Keil, Prof. Dr. +43 3842 401 ext 2821 studien.onko@lkh-leoben.at
	Klinikum Wels-Grieskirchen GmbH	Not yet recruiting
	Wels, Austria, A-4600
	Contact: Josef Thaler, Prof.Dr +43 7242 415 ext 3450 josef.thaler@klinikum-wegr.at
	Krankenhaus d. Barmherzigen Schwestern Linz	Not yet recruiting
	Linz, Austria, A-4010
	Contact: Andreas Petzer, Prof. Dr +43 732 7677 ext 4553 andreas.petzer@bhs.at
	Krankenhaus der Elisabethinen Linz	Not yet recruiting
	Linz, Austria, A-4010
	Contact: Dieter Lutz, Prof.Dr. +43 732 7676 ext 4400 dieter.lutz@elisabethinen.or.at
	Krankenhaus der Stadt Linz	Not yet recruiting
	Linz, Austria, A-4020
	Contact: Michael Fridrik, Dr. +437327806 ext 1610 michael.fridrik@akh.linz.at
	Landeskrankenhaus Feldkirch	Not yet recruiting
	Feldkirch, Austria, A-6806
	Contact: Alois Lang, Dr. +43 5522 303 ext 2301 alois.lang@lkhf.at
	Universitaetsklinik f. Innere Medizin III	Not yet recruiting
	Salzburg, Austria, A-5020
	Contact: Richard Greil, Prof. Dr. +43 662 4482 ext 2879 r.greil@salk.at

Austria, Tirol
	Medizinische Universitaet Innsbruck, Abtlg. f. Haematologie und Onkologie	Not yet recruiting
	Innsbruck, Tirol, Austria, A-6020
	Contact: Michael Steurer, Prof. Dr. +43 512 504 ext 0 michael.steurer@i-med.ac.at
	Principal Investigator: Michael Steurer, Prof. Dr.

Sponsors and Collaborators

Arbeitsgemeinschaft medikamentoese Tumortherapie

Celgene Corporation

Hoffmann-La Roche

Investigators


Principal Investigator:	Richard Greil, Prof. Dr.	Universitaetsklinik f. Innere Medizin III, Universitaetsklinikum der PMU, Salzburg

More Information

Responsible Party:	Arbeitsgemeinschaft medikamentoese Tumortherapie gemeinnuetzige GmbH ( Prof. Dr. Richard Greil )
Study ID Numbers:	CLL-5, EudraCT Nr. 2008-001430-27, ML21718
First Received:	August 20, 2008
Last Updated:	August 20, 2008
ClinicalTrials.gov Identifier:	NCT00738829
Health Authority:	Austria: Agency for Health and Food Safety; Austria: Ethikkommission

Keywords provided by Arbeitsgemeinschaft medikamentoese Tumortherapie:

CLL

untreated

immune therapy

dose escalation

maximum tolerated dose

maintenance therapy

Lenalidomide

Rituximab

Fludarabine

Study placed in the following topic categories:

Chronic lymphocytic leukemia

Leukemia, Lymphoid

Immunoproliferative Disorders

Rituximab

Lenalidomide

Fludarabine monophosphate

Leukemia

Signs and Symptoms

Lymphatic Diseases

Leukemia, Lymphocytic, Chronic, B-Cell

Fludarabine

Leukemia, B-Cell

Lymphoproliferative Disorders

Additional relevant MeSH terms:

Antimetabolites

Neoplasms by Histologic Type

Antimetabolites, Antineoplastic

Immune System Diseases

Immunologic Factors

Molecular Mechanisms of Pharmacological Action

Antineoplastic Agents

Physiological Effects of Drugs

Immunosuppressive Agents

Pharmacologic Actions

Neoplasms

Therapeutic Uses

Antirheumatic Agents

ClinicalTrials.gov processed this record on October 15, 2008

Sponsors and Collaborators:	Arbeitsgemeinschaft medikamentoese Tumortherapie Celgene Corporation Hoffmann-La Roche
Information provided by:	Arbeitsgemeinschaft medikamentoese Tumortherapie
ClinicalTrials.gov Identifier:	NCT00738829